Endogenous sex hormones homeostasis disruption combined with exogenous phthalates exposure increase the risks of childhood high blood pressure: A cohort study in China

Background: The structural similarity between sex hormones and exogenous phthalates (PAEs) enabled them as disrupters in regulating childhood blood pressure (BP). We aim to explore the association of sex hormones homeostasis and PAEs metabolites with childhood high BP (HBP). Methods: A cohort study was conducted with 1416 children aged 7–13 years at baseline and with 824, 819, and 801 children completing three waves' follow up. Serum testosterone (TT) and estradiol (E2) in children during three consecutive waves of surveys were measured by radioimmunoassay, and then TT/E2 ratio calculated as TT divided by E2 were used to represent sex hormones homeostasis. Seven urinary PAEs metabolites were measured in children of first wave. The BP Z-Scores and HBP across waves were obtained by sex, age, and height specific percentiles. Log-binomial regression models with adjusted risk ratios (aRR) after adjusting for confounders were utilized. Results: The prevalence of HBP at the baseline survey was 25.5%, and increased from 26.3% in the first wave of survey to 35.0% in the third wave of survey. PAEs were negatively correlated with E2, while positively correlated with TT and TT/E2 ratio. A positive association of the serum TT levels, TT/E2 ratio, and total PAEs was found with HBP prevalence (in wave 1, 2 and 3 with TT (aRR): 1.63, 1.37 and 1.45; with TT/E2: 1.63, 1.42 and 1.20; with PAEs: 1.40, 1.32 and 1.32), persistent HBP (with TT (aRR): 2.19; TT/E2: 2.16; PAEs: 2.57), occasional HBP (with TT (aRR): 1.94; TT/E2: 1.72; PAEs: 1.38), and new HBP incidence (with TT (aRR): 1.44; TT/E2: 1.57; PAEs: 1.67), but E2 had a negative association with HBP phenotypes (HBP prevalence in wave 1, 2 and 3 (aRR): 0.77, 0.93, and 1.10; persistent HBP: 0.47; occasional HBP: 0.96; new HBP incidence: 0.81). The E2 and PAEs had antagonistic effects on HBP risks in children, particularly in girls and those with high BMI group, but the TT levels, TT/E2 ratio and PAEs had synergistic effects on HBP risks in children, particularly in boys and those with high BMI group. Conclusion: Exogenous PAEs exposure and endogenous sex hormones homeostasis disruption independently increase the risks of HBP. Moreover, the exogenous PAEs exposure could disrupt the endogenous sex hormones homeostasis in children, thereby combinedly increased risks of childhood HBP.